Surface markers of blood lymphocytes in bronchial carcinoma

The proportion of autologous rosette-forming, i.e. autoerythrocyte-binding, T-lymphocytes, was studied in 34 patients with untreated, operable bronchial carcinoma. The number of autorosettes in patients with bronchial carcinoma was considerably below the mean value for the normal control group. In patients with metastatic involvement of the regional lymph nodes at the time of surgery the reduction in the number of autorosettes was still more marked. On the 10th postoperative day after resection of the tumour and in case of remission five months after surgery, the number of autorosettes showed a significant rise approximating the normal value. The distribution of sheep-E-rosette-forming and of the "active-early" T-lymphocytes was also studied. On the evidence of the results, the number of autorosette-forming lymphocytes lends itself to a follow-up of bronchial carcinoma by early demonstration of remissions or recurrences.     

Survivin splice variants regulate the balance between proliferation and cell death

Survivin is an inhibitor of apoptosis protein that also plays critical roles in regulating the cell cycle and mitosis. Its prominent expression in essentially all human malignancies, and low or absent expression in most normal tissues, suggests that it would be an ideal target for cancer-directed therapy. Impeding development of safe and effective survivin antagonists for clinical use is a lack of understanding of the molecular mechanisms by which survivin differentially affects apoptosis and cell division, in normal and malignant cells. We show that the diverse functional roles of survivin can be explained, in part, by its heterodimerization with survivin splice variants in tumor cells. Survivin and survivin-DeltaEx3 interact within the mitochondria where they may inhibit mitochondrial-dependent apoptosis. If the expression of all survivin forms is eliminated by siRNA transfections, cells undergo both apoptosis and defective cell division. Overall, we provide new insights suggesting that targeting specific survivin isoforms, rather than survivin alone, may selectively and effectively destroy tumor cells. These findings are likely to have a significant impact in the design of biologic agents for clinical therapy.     

Potential of endogenous estrogen receptor beta to influence the selective ER modulator ERbeta complex

The ratio of estrogen receptor beta (ERbeta) to ERalpha can alter the estrogen-like properties of tamoxifen. Transient transfection of ERbeta cDNA into cells can decrease the estrogen-like properties of the ERalpha:tamoxifen complex, whereas an increase in the amount of ERbeta is associated with tamoxifen-resistant breast cancer. We have addressed each of these hypotheses by examining well characterized laboratory models. We determined whether changes in endogenous ERbeta are responsible for the estrogen-like or antiestrogenic properties of tamoxifen or raloxifene in MDA-MB-231 cells transfected with cDNAs for ERalpha or mutants D351G, D351Y. We found that the amount of ERbeta mRNA in separate, stable transfectants of mutant ERalpha cDNA was always < 2% of ERalpha. Since at least a 50:50 mixture of ERalpha:ERbeta is needed to silence the tamoxifen:ERalpha complex, we conclude that insufficient ERbeta mRNA is available for selective ER modulation in stable transfectants of D351G and D351Y ERalpha. Similarly, to test the hypothesis that ERbeta is up-regulated and plays an important role during the development of tamoxifen-stimulated tumor growth, we quantitatively analyzed ERbeta and ERalpha mRNA in tamoxifen-na?ve (MCF-7:E2, ECC1:E2) and tamoxifen-stimulated tumors (MCF-7:TAM, EnCa 101:TAM). We found that ERbeta mRNA levels were not significantly elevated in tamoxifen-stimulated tumors and the ERalpha mRNA remained over 99% out of all ER species for all the tumors tested. The same results were also obtained when mRNA levels of ERbeta and ERalpha in a series of tamoxifen-na?ve and tamoxifen-resistant breast cancer was analyzed. We conclude that endogenous ERbeta may not play a dominant role in the modulation of the tamoxifen ERalpha complex, or in the development of tamoxifen-stimulated resistant tumor growth.     

Treatment of children's and adolescent's knee injuries

INTRODUCTION: Authors made 162 knee arthroscopic operations due to hemarthrosis of the knee, acute knee blocking or acute developed instability on patients under 18 years after knee injury during a 12 years period. The retrospective analysis of patient reports shows, that in 61.7% of the cases they found chondral- or osteochondral fracture in the knee. MATERIAL AND METHODS: On three dimensional routine X-ray pictures they were performed after the injury, in 85% of the cases fractures were not seen. Fortunately the most part of the hyalin surface injuries was smaller than 0.5 cm or were situated on less weight-bearing area only hemarthrosis evacuation and removing of loose body were done. If the osteochondral fractures was bigger than 0.5 cm or was broken from the weight-bearing surface, they were fixed by KFI or Herbert-screws. When refixation of osteochondral fracture was not possible technically or in cases of chondral fractures, primary mosaic chondroplasty was used. The correct diagnosis and the early reconstruction of injured hyalin surface in childhood and teenagers is essential regarding to the function of the knee.     

Catheter ablation for supraventricular tachycardia in children and congenital heart diseases

INTRODUCTION: Recently catheter ablation has been accepted as standard therapy for symptomatic supraventricular tachycardia in children. Nature of childhood and the variability of congenital heart diseases and congenital heart surgery distinguishes pediatric catheter ablation from the adult practice. OBJECTIVES: The aim of the present study was to summarize a single-center experience of the first 30 consecutive patients regarding the electrophysiological studies and catheter ablations, moreover to report on the national adoption of these interventions for pediatric patients in Hungary. METHODS: Between April 1996 and September 2004 catheter ablation was offered for 30 children as treatment of their supraventricular tachycardia because of failure of pharmacological therapy or parents preference. RESULTS: The mean age of the patients was 13.7 years (2.3-18.0 years) and the mean weight was 52.0 kg (12.0-81 kg). Electrophysiology study revealed 33 arrhythmogenic substrates in 30 patients, 30 of those 33 were congenital while 3 were acquired. Catheter ablation was attempted in 27 patients with acute success in 24 cases (89%). Recurrence was observed in 2 patients and the redo ablation was effective in both, although a second recurrence occurred later in one of them. There were no major complications, but two minor ones (pseudoaneurysm of arteria femoralis, transient ventricular ectopy) occurred. CONCLUSIONS: Catheter ablation is safe and effective in children with congenital heart disease. Our results are comparable with the international data.     

The environmental estrogen bisphenol a inhibits estradiol-induced hippocampal synaptogenesis

Bisphenol A (BPA) is an estrogenic chemical that is widely used in the manufacture of plastics and epoxy resins. Because BPA leaches out of plastic food and drink containers, as well as the BPA-containing plastics used in dental prostheses and sealants, considerable potential exists for human exposure to this compound. In this article we show that treatment of ovariectomized rats with BPA dose-dependently inhibits the estrogen-induced formation of dendritic spine synapses on pyramidal neurons in the CA1 area of the hippocampus. Significant inhibitory effects of BPA were observed at a dose of only 40 microg/kg, below the current U.S. Environmental Protection Agency reference daily limit for human exposure. Because synaptic remodeling has been postulated to contribute to the rapid effects of estrogen on hippocampus-dependent memory, these data suggest that environmental BPA exposure may interfere with the development and expression of normal sex differences in cognitive function, via inhibition of estrogen-dependent hippocampal synapse formation. It may also exacerbate the impairment of hippocampal function observed during normal aging, as endogenous estrogen production declines.     

Determinant role of education in the ethical aspects of resuscitation: a German/Hungarian comparison

Introduction, objectives: Bioethical principles concerning Do Not Attempt Resuscitation (DNAR) orders are connected significantly with education according to our previous investigation. In order to confirm the hypothesis, Hungarian results were compared with the data gained from a highly qualified homogeneous group of German doctors, showing similar cultural traditions. Methods: The questionnaire investigated the factors influencing DNAR orders as functions of intensive medical experience, ideological view and professional education, using a 5-point visual analogue scale. Answers were assigned to categories of autonomy, futility, obtainable quality of life, resource utilization and a category of other factors detailed later. Results: The DNAR decision and termination of resuscitation are to almost the same extent determined by futility (3.29+-0.75; 3.49+-0.71) and obtainable quality of life (3.13+-1.31; 3.47+-1.34). The opinion of head of department was also important (3.24+-1.35; 3.23+-1.36). Patient's autonomy played an important role (3.15+-0.85; 2.36+-1.48) in decision making. In comparison with the Hungarian results, the only significant difference was found in the field of patient's autonomy in both not starting (p<0.0002) and terminating resuscitation (p<0.02) in favour of German doctors respecting it. Discussion: The results support the original hypothesis that consideration of modern bioethical principles, and especially the patient's autonomy are related to the level of the doctor's education. Comparing to Hungarian data there is only a minimal difference in other bioethical points, while the population of German doctors interviewed appreciated the patient's autonomy significantly higher. There should be greater discussion of ethical considerations in cardiopulmonary resuscitation education.     

Simultaneous bilateral percutaneous nephrolithotomy in children

In the paediatric section, two papers relating to the upper urinary tract are presented. The first, from Hungary, describes simultaneous bilateral percutaneous nephrolithotomy in 13 patients, where it was deemed feasible; this is the first such report. Authors from London report on unilateral nephrectomy in patients with nephrogenic hypertension, and found that it was successful in normalising blood pressure in patients with renal hypertension with a normal contralateral kidney. OBJECTIVE: To evaluate the efficacy of removing bilateral kidney stones simultaneously from children, in one session. PATIENTS AND METHODS: Thirteen patients (three girls and 10 boys, 26 kidneys; mean age 8 years, range 3-14) underwent simultaneous bilateral percutaneous nephrolithotomy (PCNL) in the same session, under general anaesthesia, starting with ureteric catheter insertion into both kidneys and using a 26 F adult nephroscope. The mean (range) stone diameter was 2 (1-3.5) cm. Three patients had staghorn stones in one of their kidneys. Ultrasonic disintegration was used; two patients had bilateral and two others unilateral endopylotomy, and one patient had percutaneous suprapubic cystolithotomy in the same session. The mean (range) operative duration was 65 (55-90) min. RESULTS: All patients were rendered stone-free; there was no severe bleeding or any other complication. On one side in one of the patients, a second session was needed because of residual stone. The nephrostomy tubes were removed 3 and 4 days after PCNL and the hospital stay was 6 (1-11) days. CONCLUSION: The advantages of simultaneous bilateral PCNL are reduced psychological stress, one cystoscopy and anaesthesia, less medication and a shorter hospital stay and convalescence, with considerable savings in cost. In experienced hands this method can be used not only in adults but also in children. To our knowledge this is the only report of this technique in children.     

Poly(adenosine diphosphate ribose) polymerase inhibition modulates spinal cord dysfunction after thoracoabdominal aortic ischemia-reperfusion

OBJECTIVE: Spinal cord injury (SCI) remains a source of morbidity after thoracoabdominal aortic reconstruction. These studies were designed to determine whether PJ34, a novel ultrapotent inhibitor of the nuclear enzyme poly(adenosine diphosphate ribose) polymerase (PARP) could modulate neurologic injury after thoracic aortic ischemia reperfusion (TAR) in a murine model of SCI. METHODS: Forty-one anesthetized male mice were subject to thoracic aortic occlusion (11 minutes) through a cervical mediastinotomy followed by 48 hours of reperfusion (TAR) under normothermic conditions. PJ34-treated mice (PJ, n = 12) were given 10 mg/kg PJ34 intraperitoneally 1 hour before ischemia and 1 hour after unclamping. The control group (UN, n = 21) received normal saline intraperitoneally 1 hour before ischemia and 1 hour after unclamping. Sham animals (n = 10) were subject to thoracic aortic exposure with no aortic clamping and similar intraperitoneal normal saline injections. PARP-1-/- (KO, n = 8) mice were subjected to the same conditions as the UN mice. Blinded observers rated murine neurologic status after TAR by using an established rodent paralysis scoring system. Murine spinal cords were subjected to cytokine (GRO-1) protein analysis as a marker of inflammation and immunohistochemical analysis (hematoxylin-eosin and PAR staining). Paralysis scores (PS) and GRO-1 levels were compared with analysis of variance, and survival data were compared with chi 2 . RESULTS: Immediately after TAR, UN and PJ mice had severe neurologic dysfunction (PS = 5.8 +/- 0.1 and 4.6 +/- 0.6, respectively; P > .05), which was significantly worse than the KO mice (PS = 1.0 +/- 0.7, P < .001). After 6, 24, and 48 hours KO mice had no discernable neurologic injury (PS = 0). Six hours after TAR, PJ mice significantly improved (PS = 1.1 +/- 0.73, P < .001) and remained improved at 24 (PS = 0.7 +/- 0.6) and 48 hours (PS = 0.6 +/- 0.6). UN mice did not improve their PS, and Sham mice showed no neurologic abnormality at any time during these experiments. The mortality at 48 hours was 0% for PJ and KO mice, 43% for UN (P = .012), and 0% for Sham. GRO-1 levels were significantly decreased in PJ and KO versus UN mice (UN, 583 +/- 119 vs PJ, 5.8 +/- 0 vs KO, 5.3 +/- 1.4 mg/pg; P < .0001). Immunohistochemistry showed evidence of decreased PAR staining and ventral motor neuron injury in PJ mice. CONCLUSIONS: Genetic deletion of PARP or inhibition of its activity (PJ34) rescued neurologic function in mice subjected to TAR. PARP inhibition might represent a novel therapeutic approach for prevention of SCI after TAR.